This project consists of an in vivo, non-invasive investigation of dental pulp cooling, followed by a histological and reversed-phase high performance liquid chromatographic (RP-HPLC) and radioimmunoassay investigation into pulpal neurotransmitters, neuroregulators, and inflammatory regulators as they relate to lowering of pulp temperatures. The specific aims are to initially evaluate the performance of a pulpal cooling device through its application in the M. fascicularis monkey. The device will then be used to determine neural and microcirculatory response non-invasively in humans through concurrent use of a constant current pulp tester and a laser Doppler flow cytometer (LDFC). The response of neurotransmitters, neuroregulators and inflammatory mediators in response to cooling will be examined next. The experimental design involves testing the safety of the device in vivo by applying it to a test animal and examining the tissue histologically for the presence or absence of an inflammatory response. Once it has been established that the device will not harm the pulp, it will be used to alter or abolish interdental nerve activity while evaluating its effect on pulpal microcirculation. The device will be applied to humans to lower pulp temperatures. Concurrent electric pulp testing will be used to assess the levels at which interdental nerve response is altered. Pulpal temperatures will then be lowered to those same levels, while pulpal blood flow is assessed with LDFC. The presence of neurovascular regulators and inflammatory mediators in response to pulp cooling will be identified and quantified by use of RP-HPLC after application of the cooling device in the M. fascicularis monkey. Test results will provide the basis for a cooling device that can be adopted for use clinically to obviate the need of local anesthetics and prevent untoward reactions to dental preparation and restoration procedures.